Stress responsiveness of hypothalamic corticotrophin-releasing factor and pituitary pro-opiomelanocortin mRNAs following high-dose glucocorticoid treatment and withdrawal in the rat.
In-situ hybridization with synthetic oligonucleotide probes was used to determine the mRNA content of corticotrophin-releasing factor (CRF) and proenkephalin A mRNA in the paraventricular nucleus, and of pro-opiomelanocortin (POMC) mRNA in the anterior pituitary gland of male rats immediately after, and during recovery from, chronic high-dose prednisolone treatment. Levels of transcripts for mRNA for both CRF and POMC were markedly reduced after the treatment, but there was a rapid return to control values for CRF mRNA within 18 h of steroid withdrawal. In untreated animals, the stressful stimulus of i.p. hypertonic saline increased CRF and proenkephalin A mRNA within 4 h with no significant difference in response seen whether the tissues were removed at 13.00 or 20.00 h. The increase in POMC mRNA did not reach statistical significance in these animals. Although prednisolone resulted in a marked reduction of basal CRF mRNA, the stress-induced increment of CRF mRNA remained comparable with that found in untreated animals. On the day following cessation of prednisolone treatment at 09.00 h, basal and stress levels of CRF mRNA were significantly higher in rats killed at 20.00 h than at 13.00 h. Proenkephalin A mRNA transcripts were below quantifiable levels of detection in control or non-stressed prednisolone-treated animals at all the time-points studied. Stress, however, resulted in the accumulation of proenkephalin A mRNA in control animals. This response was inhibited by prednisolone treatment and only returned 18 h after withdrawal. Prednisolone treatment reduced POMC mRNA below the levels detected in untreated animals, with no detectable response to stress.(ABSTRACT TRUNCATED AT 250 WORDS)
Harbuz
M S
MS
Neuroendocrinology Unit, Charing Cross and Westminster Medical School, London.
Nicholson
S A
SA
Gillham
B
B
Lightman
S L
SL
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000235:genetics*; D004745:Enkephalins / Q000235:genetics; D008297:Male; D015336:Molecular Probe Techniques; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000502:physiology; D011239:Prednisolone / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D011333:Pro-Opiomelanocortin / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains; D012462:Saline Solution, Hypertonic / Q000494:pharmacology; D013495:Supraoptic Nucleus / Q000187:drug effects* / Q000502:physiology
D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; D012462:Saline Solution, Hypertonic; C029992:proenkephalin; D011333:Pro-Opiomelanocortin; D003346:Corticotropin-Releasing Hormone; D011239:Prednisolone; C021322:prednisolone hemisuccinate